Role of local angiotensin II signaling in bladder function

Abstract

Angiotensin II signaling plays a crucial role in many different diseases. Although it has been known for several decades that local angiotensin II signaling molecules are present in the bladder, the understanding of their functions there is still limited, especially compared with other organ systems such as cardiovascular and respiratory systems. This article reviews current literature regarding local angiotensin II signaling in the urinary bladder. By reviewing several decades of literature, the field has provided strong evidence to support the presence of local angiotensin II signaling in the bladder, including the expression of angiotensin type 1 receptor and angiotensin type 2 receptor in both human and animal tissues. In addition, evidence suggests a functional role of angiotensin type 1 receptor in mediating bladder contractions. In bladder disease models, angiotensin II signaling can be upregulated, and angiotensin type 1 receptor activity is associated with increases in inflammation, fibrosis, and oxidative stress. We also address the gaps in knowledge that remain in understanding local angiotensin II signaling in the bladder, including limitations on clinical translatability. Although there is a strong foundation regarding the local presence and role of angiotensin II signaling in the bladder, further research is needed to support translational applications.

Keywords: angiotensin; bladder; physiology; receptor; signaling.

Graphical abstract

Figure 1.

Summary of AT₁R and AT₂R expression in the bladder. AT₁R (blue) expression is found in urothelial cells, fibroblasts, and bladder smooth muscle cells. AT₂R (orange) has been found in fibroblasts and smooth muscle. ^aRef. ; ^bRef. ; ^cRef. . AT₁R, angiotensin II type 1 receptor; AT₂R, angiotensin II type 2 receptor.

Figure 2.

Summary of the major roles of local ANG II signaling in the bladder. In addition to circulatory production and stretch-induced release, ANG II is produced locally in the bladder. ANG II is formed locally from ANG I via chymase and/or ACE. ANG II binds with two of its G protein-coupled receptors, AT₁R and AT₂R. AT₁R mediates contractility and may be upregulated with age and outlet obstruction. Although AT₂R may attenuate the actions of AT₁R, its functions are widely unknown. ARBs, by blocking AT₁R, have shown a reduction of negative effects in the bladder in animal models of disease. ^aRefs. and ; ^bRefs. and ; ^cRefs. and , ^dRefs. , , and ; ^eRef. ; ^fRefs. , , , , , and –; ^gRefs. and ; ^hRefs. and ; ⁱRefs. and ; ^jRefs. , , , , , and ; ^kRefs. , , and ; ^lRef. . ACE, angiotensin-converting enzyme; ANG I, angiotensin I; ANG II, angiotensin II; ARBs, angiotensin receptor blockers; AT₁R, ANG II type 1 receptor; AT₂R, ANG II type 2 receptor.